Predicting Hot Spot Residues at Protein-DNA Binding Interfaces Based on Sequence Information

Hot spot residues at protein-DNA binding interfaces are hugely important for investigating the underlying mechanism of molecular recognition. Currently, there are a few tools available for identifying the hot spot residues in the protein-DNA complexes. In addition, the three-dimensional protein structures are needed in these tools. However, it is well known that the three-dimensional structures are unavailable for most proteins. Considering the limitation, we proposed a method, named SPDH, for predicting hot spot residues only based on protein sequences. Firstly, we obtained 133 features from physicochemical property, conservation, predicted solvent accessible surface area and structure. Then, we systematically assessed these features based on various feature selection methods to obtain the optimal feature subset and compared the models using four classical machine learning algorithms (support vector machine, random forest, logistic regression, and k-nearest neighbor) on the training dataset. We found that the variability of physicochemical property features between wild and mutative types was important on improving the performance of the prediction model. On the independent test set, our method achieved the performance with AUC of 0.760 and sensitivity of 0.808, and outperformed other methods. The data and source code can be downloaded at https://github.com/xialab-ahu/SPDH .